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1.
PLoS Pathog ; 20(3): e1012104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38512977

RESUMO

The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Camundongos , Receptores ErbB/metabolismo , Febre Aftosa/genética , Vírus da Febre Aftosa/genética , Regulação da Expressão Gênica , RNA Guia de Sistemas CRISPR-Cas , Suínos
2.
Proc Natl Acad Sci U S A ; 120(5): e2210651120, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36689664

RESUMO

Millions of years of evolution have allowed animals to develop unusual locomotion capabilities. A striking example is the legless-jumping of click beetles and trap-jaw ants, which jump more than 10 times their body length. Their delicate musculoskeletal system amplifies their muscles' power. It is challenging to engineer insect-scale jumpers that use onboard actuators for both elastic energy storage and power amplification. Typical jumpers require a combination of at least two actuator mechanisms for elastic energy storage and jump triggering, leading to complex designs having many parts. Here, we report the new concept of dynamic buckling cascading, in which a single unidirectional actuation stroke drives an elastic beam through a sequence of energy-storing buckling modes automatically followed by spontaneous impulsive snapping at a critical triggering threshold. Integrating this cascade in a robot enables jumping with unidirectional muscles and power amplification (JUMPA). These JUMPA systems use a single lightweight mechanism for energy storage and release with a mass of 1.6 g and 2 cm length and jump up to 0.9 m, 40 times their body length. They jump repeatedly by reengaging the latch and using coiled artificial muscles to restore elastic energy. The robots reach their performance limits guided by theoretical analysis of snap-through and momentum exchange during ground collision. These jumpers reach the energy densities typical of the best macroscale jumping robots, while also matching the rapid escape times of jumping insects, thus demonstrating the path toward future applications including proximity sensing, inspection, and search and rescue.


Assuntos
Formigas , Besouros , Robótica , Animais , Locomoção/fisiologia , Músculos , Fenômenos Biomecânicos
3.
BMC Genomics ; 25(1): 494, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764031

RESUMO

BACKGROUND: Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development. RESULTS: In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment. CONCLUSIONS: These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Glândulas Mamárias Animais , Animais , Feminino , Camundongos , Apoptose/genética , Proliferação de Células , Células Epiteliais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Transdução de Sinais , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo
4.
J Am Chem Soc ; 146(37): 25433-25438, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39248664

RESUMO

We report a new supramolecular porous crystal assembled from fused macrocycle-cage molecules. The molecule comprises a prismatic cage with three macrocycles radially attached. The molecules form a nanoporous crystal with one-dimensional (1D) nanochannels. The supramolecular porous crystal can take up lithium-ion electrolytes and achieve an ionic conductivity of up to 8.3 × 10-4 S/cm. Structural analysis and density functional theory calculations reveal that efficient Li-ion electrolyte uptake, the presence of 1D nanochannels, and weak interactions between lithium ions and the crystal enable fast lithium-ion transport. Our findings demonstrate the potential of fused macrocycle-cage molecules as a new design motif for ion-conducting molecular crystals.

5.
Opt Lett ; 49(6): 1567-1570, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489452

RESUMO

Speckle patterns generated as coherent optical beams are reflected by scattering elements. Multimode fibers (MMFs) can modify the transverse intensity distribution of speckle patterns with macro perturbations, i.e., pressures, providing a simple and low-cost way to achieve equivalent beam-steering for indoor optical wireless communications (OWCs) with divergent optical beams. However, the received optical power (ROP) variance severely limits the mobility of user terminals. In this paper, the issue is alleviated by using the overfilled launch of MMFs and the diversity gain of multi-receivers. By adjusting the axial spatial coupling distance between the MMF and the single mode fiber (SMF) emitting coherent laser, the number of excited modes of MMF can be significantly increased at 1550 nm with negligible coupling and bending losses. In addition, the signal-to-noise ratio (SNR) enhancement obtained by applying two receivers is theoretically analyzed for the case when either thermal noise or shot noise is dominant. The experimental results demonstrate that the proposed scheme can efficiently compensate for the ROP inhomogeneity, and at the same time it can extend the achievable full steering angle up to 12° at a 1.5-m free-space distance for bit error rate (BER) values of less than 3.8 × 10-3.

6.
Phys Rev Lett ; 132(26): 267201, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38996296

RESUMO

A snap-through bifurcation occurs when a bistable structure loses one of its stable states and moves rapidly to the remaining state. For example, a buckled arch with symmetrically clamped ends can snap between an inverted and a natural state as the ends are released. A standard linear stability analysis suggests that the arch becomes unstable to asymmetric perturbations. Surprisingly, our experiments show that this is not always the case: symmetric transitions are also observed. Using experiments, numerics, and a toy model, we show that the symmetry of the transition depends on the rate at which the ends are released, with sufficiently fast loading leading to symmetric snap-through. Our toy model reveals that this behavior is caused by a region of the system's state space in which any initial asymmetry is amplified. The system may not enter this region when loaded fast (hence remaining symmetric), but will traverse it for some interval of time when loaded slowly, causing a transient amplification of asymmetry. Our toy model suggests that this behavior is not unique to snapping arches, but rather can be observed in dynamical systems where both a saddle-node and a pitchfork bifurcation occur in close proximity.

7.
J Magn Reson Imaging ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39311711

RESUMO

BACKGROUND: Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness, is associated with neurodegeneration in the visual pathway, but the underlying pathophysiology remains incompletely resolved. PURPOSE: To characterize macro- and microstructural white matter abnormalities in optic tract (OT) and optic radiation (OR) of POAG. STUDY TYPE: Prospective. POPULATIONS: A total of 34 POAG patients (21 males, 13 females) and 25 healthy controls (HCs) (16 males, nine females). FIELD STRENGTH/SEQUENCE: 3 T; multiband spin-echo echo planar diffusion spectrum imaging (DSI). ASSESSMENT: We compared multiple morphology metrics, including volume, area, length, and shape metrics, as well as diffusion metrics such as diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity, radial diffusivity, and axial diffusivity), mean apparent propagator (mean squared displacement, q-space inverse variance, return-to-origin probability, return-to-axis probabilities [RTAP] and return-to-plane probabilities, non-Gaussianity, perpendicular non-Gaussianity, parallel non-Gaussianity), and neurite orientation dispersion and density imaging (intracellular volume fraction, orientation dispersion index [ODI], and isotropic volume fraction of the OT and OR). STATISTICAL TESTS: Statistical comparisons and classifications employed linear mixed model and logistic regression. Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). P-value <0.05 was statistically significant. RESULTS: Morphology analysis in POAG revealed a lower span in the OR (29.43 ± 2.30 vs. 30.59 ± 2.01, 3.8%) and OT (19.73 ± 2.21 vs. 20.68 ± 1.37, 4.6%), and a higher curl (3.03 ± 0.22 vs. 2.90 ± 0.16, 4.5%) in OT. Diffusion metrics revealed lower mean FA (OR: 0.328 ± 0.03 vs. 0.340 ± 0.018, 3.5%; OT: 0.255 ± 0.022 vs. 0.268 ± 0.018, 4.9%) and lower mean RTAP (OR: 5.919 ± 0.529 vs. 6.216 ± 0.489, 4.8%; OT: 4.089 ± 0.402 vs. 4.280 ± 0.353, 4.5%), with higher mean ODI in the OT (0.448 ± 0.029 vs. 0.433 ± 0.025, 3.5%). Combined models, incorporating these MRI metrics, effectively discriminated POAG from HCs, achieving AUCs of 0.84 for OR and 0.83 for OT. DATA CONCLUSIONS: DSI-derived morphology and diffusion metrics demonstrated macro- and micro abnormalities in the visual pathway, providing insights into POAG-related neurodegeneration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

8.
J Chem Inf Model ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266056

RESUMO

Despite the exciting progress in target-specific de novo protein binder design, peptide binder design remains challenging due to the flexibility of peptide structures and the scarcity of protein-peptide complex structure data. In this study, we curated a large synthetic data set, referred to as PepPC-F, from the abundant protein-protein interface data and developed DiffPepBuilder, a de novo target-specific peptide binder generation method that utilizes an SE(3)-equivariant diffusion model trained on PepPC-F to codesign peptide sequences and structures. DiffPepBuilder also introduces disulfide bonds to stabilize the generated peptide structures. We tested DiffPepBuilder on 30 experimentally verified strong peptide binders with available protein-peptide complex structures. DiffPepBuilder was able to effectively recall the native structures and sequences of the peptide ligands and to generate novel peptide binders with improved binding free energy. We subsequently conducted de novo generation case studies on three targets. In both the regeneration test and case studies, DiffPepBuilder outperformed AfDesign and RFdiffusion coupled with ProteinMPNN, in terms of sequence and structure recall, interface quality, and structural diversity. Molecular dynamics simulations confirmed that the introduction of disulfide bonds enhanced the structural rigidity and binding performance of the generated peptides. As a general peptide binder de novo design tool, DiffPepBuilder can be used to design peptide binders for given protein targets with three-dimensional and binding site information.

9.
Proc Natl Acad Sci U S A ; 118(32)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34353904

RESUMO

The parathyroid hormone receptor 2 (PTH2R) is a class B1 G protein-coupled receptor (GPCR) involved in the regulation of calcium transport, nociception mediation, and wound healing. Naturally occurring mutations in PTH2R were reported to cause hereditary diseases, including syndromic short stature. Here, we report the cryogenic electron microscopy structure of PTH2R bound to its endogenous ligand, tuberoinfundibular peptide (TIP39), and a heterotrimeric Gs protein at a global resolution of 2.8 Å. The structure reveals that TIP39 adopts a unique loop conformation at the N terminus and deeply inserts into the orthosteric ligand-binding pocket in the transmembrane domain. Molecular dynamics simulation and site-directed mutagenesis studies uncover the basis of ligand specificity relative to three PTH2R agonists, TIP39, PTH, and PTH-related peptide. We also compare the action of TIP39 with an antagonist lacking six residues from the peptide N terminus, TIP(7-39), which underscores the indispensable role of the N terminus of TIP39 in PTH2R activation. Additionally, we unveil that a disease-associated mutation G258D significantly diminished cAMP accumulation induced by TIP39. Together, these results not only provide structural insights into ligand specificity and receptor activation of class B1 GPCRs but also offer a foundation to systematically rationalize the available pharmacological data to develop therapies for various disorders associated with PTH2R.


Assuntos
Receptor Tipo 2 de Hormônio Paratireóideo/química , Receptor Tipo 2 de Hormônio Paratireóideo/metabolismo , Sítios de Ligação , Microscopia Crioeletrônica , AMP Cíclico/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Humanos , Ligantes , Simulação de Dinâmica Molecular , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Mutação , Neuropeptídeos/química , Neuropeptídeos/metabolismo , Conformação Proteica , Receptor Tipo 2 de Hormônio Paratireóideo/genética
10.
Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34599099

RESUMO

Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates Gs while SV1 selectively couples to ß-arrestins. Based on the cryogenic electron microscopy structures of SV1 in the apo state or GHRH-bound state in complex with the Gs protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, Gs versus ß-arrestins. As suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias toward ß-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation.


Assuntos
Processamento Alternativo/genética , Variação Genética/genética , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Cultivadas , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases/genética , Células PC-3 , Células Sf9 , Transdução de Sinais/genética , beta-Arrestinas/genética
11.
Sensors (Basel) ; 24(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732965

RESUMO

Although the rapid expansion of urban rail transit offers convenience to citizens, the issue of subway vibration cannot be overlooked. This study investigates the spatial distribution characteristics of vibration in the Fayuan Temple historic and cultural reserve. It involves using a V001 magnetoelectric acceleration sensor capable of monitoring low amplitudes with a sensitivity of 0.298 V/(m/s2), a measuring range of up to 20 m/s2, and a frequency range span from 0.5 to 100 Hz for in situ testing, analyzing the law of vibration propagation in this area, evaluating the impact on buildings, and determining the vibration reduction scheme. The reserve is divided into three zones based on the vertical vibration level measured during the in situ test as follows: severely excessive, generally excessive, and non-excessive vibration. Furthermore, the research develops a dynamic coupling model of vehicle-track-tunnel-stratum-structure to verify the damping effect of the wire spring floating plate track and periodic pile row. It compares the characteristics of three vibration reduction schemes, namely, internal vibration reduction reconstruction, periodic pile row, and anti-vibration reinforcement or reconstruction of buildings, proposing a comprehensive solution. Considering the construction conditions, difficulty, cost, and other factors, a periodic pile row is recommended as the primary treatment measure. If necessary, anti-vibration reinforcement or reconstruction of buildings can serve as supplemental measures.

12.
Angew Chem Int Ed Engl ; 63(1): e202315314, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38009311

RESUMO

Aprotic Li-O2 battery has attracted considerable interest for high theoretical energy density, however the disproportionation of the intermediate of superoxide (O2 - ) during discharge and charge leads to slow reaction kinetics and large voltage hysteresis. Herein, the chemically stable ruthenium tris(bipyridine) (RB) cations are employed as a soluble catalyst to alternate the pathway of O2 - disproportionation and its kinetics in both the discharge and charge processes. RB captures O2 - dimer and promotes their intramolecular charge transfer, and it decreases the energy barrier of the disproportionation reaction from 7.70 to 0.70 kcal mol-1 . This facilitates the discharge and charge processes and simultaneously mitigates O2 - and singlet oxygen related side reactions. These endow the Li-O2 battery with reduced discharge/charge voltage gap of 0.72 V and prolonged lifespan for over 230 cycles when coupled with RuO2 catalyst. This work highlights the vital role of superoxide disproportionation for Li-O2 battery.

13.
Mol Biol Evol ; 39(4)2022 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-35325213

RESUMO

The gene numbers and evolutionary rates of birds were assumed to be much lower than those of mammals, which is in sharp contrast to the huge species number and morphological diversity of birds. It is, therefore, necessary to construct a complete avian genome and analyze its evolution. We constructed a chicken pan-genome from 20 de novo assembled genomes with high sequencing depth, and identified 1,335 protein-coding genes and 3,011 long noncoding RNAs not found in GRCg6a. The majority of these novel genes were detected across most individuals of the examined transcriptomes but were seldomly measured in each of the DNA sequencing data regardless of Illumina or PacBio technology. Furthermore, different from previous pan-genome models, most of these novel genes were overrepresented on chromosomal subtelomeric regions and microchromosomes, surrounded by extremely high proportions of tandem repeats, which strongly blocks DNA sequencing. These hidden genes were proved to be shared by all chicken genomes, included many housekeeping genes, and enriched in immune pathways. Comparative genomics revealed the novel genes had 3-fold elevated substitution rates than known ones, updating the knowledge about evolutionary rates in birds. Our study provides a framework for constructing a better chicken genome, which will contribute toward the understanding of avian evolution and the improvement of poultry breeding.


Assuntos
Galinhas , Genoma , Animais , Galinhas/genética , Genômica , Mamíferos/genética , Análise de Sequência de DNA
14.
Eur Radiol ; 33(12): 9052-9062, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37405505

RESUMO

OBJECTIVES: To evaluate the predictive performance of pretreatment dual-energy CT (DECT) for early response to induction chemotherapy and survival in nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 56 NPC patients who underwent pretreatment DECT scans with posttreatment follow-up were enrolled. The DECT-derived normalised iodine concentration (nIC), effective atomic number (Zeff), 40-180 keV (20 keV interval), and Mix-0.3 value of the tumour lesions were measured to predict the early response to induction chemotherapy and survival in nasopharyngeal carcinoma. The Mann‒Whitney U test, ROC analysis, Kaplan‒Meier method with log-rank test, and Cox proportional hazards model were performed to evaluate the predictive performance of DECT parameters, respectively. RESULTS: Among all DECT-derived parameters, ROC analysis showed the predictive performances of nIC and Zeff values for early objective response to induction chemotherapy (AUCs of 0.803 and 0.826), locoregional failure-free survival (AUCs of 0.786 and 0.767), progression-free survival (AUCs of 0.856 and 0.731) and overall survival (AUCs of 0.765 and 0.799) in NPC patients, respectively (all p < 0.05). Moreover, multivariate analysis showed that a high nIC value was an independent predictor of poor survival in NPC. In addition, survival analysis indicated that NPC patients with higher nIC values in primary tumours tend to have lower 5-year locoregional failure-free survival, progression-free survival and overall survival rates than those with lower nIC values. CONCLUSIONS: DECT-derived nIC and Zeff values can predict early response to induction chemotherapy and survival in NPC; in particular, a high nIC value is an independent predictive factor of poor survival in NPC. CLINICAL RELEVANCE STATEMENT: Preoperative dual-energy computed tomography may provide predictive value for early response and survival outcomes in patients with nasopharyngeal carcinoma, and facilitate their clinical management. KEY POINTS: • Pretreatment dual-energy computed tomography helps to predict early response to therapy and survival in NPC. • NIC and Zeff values derived from dual-energy computed tomography can predict early objective response to induction chemotherapy and survival in NPC. • A high nIC value is an independent predictive factor of poor survival in NPC.


Assuntos
Quimioterapia de Indução , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Estudos Retrospectivos , Quimioterapia de Indução/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico
15.
Macromol Rapid Commun ; 44(7): e2200814, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36459585

RESUMO

Excessive exudate secreted from diabetic wounds often results in skin overhydration, severe infections, and secondary damage upon dressing changes. However, conventional wound dressings are difficult to synchronously realize the non-maceration of wound sites and rapid exudate transport due to their random porous structure. Herein, a self-pumping Janus hydrogel with aligned channels (JHA) composed of hydrophilic poly (ethylene glycol) diacrylate (PEGDA) hydrogel layer and hydrophobic polyurethane (PU)/graphene oxide (GO)/polytetrafluoroethylene (PTFE) layer is designed to rapidly export exudate and accelerate diabetic wound healing. In the design, the ice-templating process endows the hydrophilic hydrogel layer with superior liquid transport ability and mechanical strength due to the formation of aligned channel structure. The hydrophobic layer with controlled thickness functions as an effective barrier to prevent exudate from wetting the skin surface. Experiments in diabetic rat model show that JHA can significantly promote re-epithelialization and collagen deposition, shorten the inflammation phase, and accelerate wound healing. This unique JHA dressing may have great potential for real-life usage in clinical patients.


Assuntos
Diabetes Mellitus , Hidrogéis , Ratos , Animais , Hidrogéis/química , Cicatrização , Pele
16.
Genet Sel Evol ; 55(1): 72, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853325

RESUMO

BACKGROUND: Although the accumulation of whole-genome sequencing (WGS) data has accelerated the identification of mutations underlying complex traits, its impact on the accuracy of genomic predictions is limited. Reliable genotyping data and pre-selected beneficial loci can be used to improve prediction accuracy. Previously, we reported a low-coverage sequencing genotyping method that yielded 11.3 million highly accurate single-nucleotide polymorphisms (SNPs) in pigs. Here, we introduce a method termed selective linkage disequilibrium pruning (SLDP), which refines the set of SNPs that show a large gain during prediction of complex traits using whole-genome SNP data. RESULTS: We used the SLDP method to identify and select markers among millions of SNPs based on genome-wide association study (GWAS) prior information. We evaluated the performance of SLDP with respect to three real traits and six simulated traits with varying genetic architectures using two representative models (genomic best linear unbiased prediction and BayesR) on samples from 3579 Duroc boars. SLDP was determined by testing 180 combinations of two core parameters (GWAS P-value thresholds and linkage disequilibrium r2). The parameters for each trait were optimized in the training population by five fold cross-validation and then tested in the validation population. Similar to previous GWAS prior-based methods, the performance of SLDP was mainly affected by the genetic architecture of the traits analyzed. Specifically, SLDP performed better for traits controlled by major quantitative trait loci (QTL) or a small number of quantitative trait nucleotides (QTN). Compared with two commercial SNP chips, genotyping-by-sequencing data, and an unselected whole-genome SNP panel, the SLDP strategy led to significant improvements in prediction accuracy, which ranged from 0.84 to 3.22% for real traits controlled by major or moderate QTL and from 1.23 to 11.47% for simulated traits controlled by a small number of QTN. CONCLUSIONS: The SLDP marker selection method can be incorporated into mainstream prediction models to yield accuracy improvements for traits with a relatively simple genetic architecture, however, it has no significant advantage for traits not controlled by major QTL. The main factors that affect its performance are the genetic architecture of traits and the reliability of GWAS prior information. Our findings can facilitate the application of WGS-based genomic selection.


Assuntos
Estudo de Associação Genômica Ampla , Genômica , Animais , Suínos/genética , Masculino , Desequilíbrio de Ligação , Genótipo , Estudo de Associação Genômica Ampla/métodos , Reprodutibilidade dos Testes , Genômica/métodos , Fenótipo , Locos de Características Quantitativas , Polimorfismo de Nucleotídeo Único
17.
J Comput Assist Tomogr ; 47(6): 989-995, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37948376

RESUMO

PURPOSE: This study aimed to evaluate the imaging features of maxillary sinus adenoid cystic carcinoma (ACC) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate the imaging differences between solid and nonsolid maxillary sinus ACC. METHODS: We retrospectively reviewed 40 cases of histopathologically confirmed ACC of the maxillary sinus. All the patients underwent CT and MRI. Based on the histopathological characteristics, the patients were classified into 2 groups: ( a ) solid maxillary sinus ACC (n = 16) and ( b ) nonsolid maxillary sinus ACC (n = 24). Imaging features such as tumor size, morphology, internal structure, margin, type of bone destruction, signal intensity, enhancement changes, and perineural tumor spread on CT and MRI, were evaluated. The apparent diffusion coefficient (ADC) was measured. Comparisons of imaging features and ADC values were performed between the solid and nonsolid maxillary sinus ACC using χ 2 and nonparametric tests. RESULTS: The internal structure, margin, type of bone destruction, and degree of enhancement significantly differed between solid and nonsolid maxillary sinus ACC (all P < 0.05). The ADC of the solid maxillary sinus ACC was considerably lower than that of the nonsolid maxillary sinus ( P < 0.05). CONCLUSIONS: Computed tomography and MRI may aid in the differentiation of solid and nonsolid types of maxillary sinus ACC.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias dos Seios Paranasais , Humanos , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/patologia , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos
18.
Neurol Sci ; 44(8): 2915-2922, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36869275

RESUMO

PURPOSE: To explore the alterations of whole brain functional network using the degree centrality (DC) analysis in neovascular glaucoma (NVG) and the correlation between DC values and NVG clinical indices. MATERIALS AND METHODS: Twenty NVG patients and twenty normal controls (NC), closely matched in age, sex, and education, were recruited for this study. All subjects underwent comprehensive ophthalmologic examinations and a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The differences in DC values of brain network between NVG and NC groups were analyzed, and correlation analysis was performed to explore the relationships between DC values and clinical ophthalmological indices in NVG group. RESULTS: Compared with NC group, significantly decreased DC values were found in the left superior occipital gyrus and left postcentral gyrus, while significantly increased DC values in the right anterior cingulate gyrus and left medial frontal gyrus in NVG group. (All P < 0.05, FDR corrected). In the NVG group, the DC value in left superior occipital gyrus showed significantly positive correlations with retinal nerve fiber layer (RNFL) thickness (R = 0.484, P = 0.031) and mean deviation of visual field (MDVF) (R = 0.678, P = 0.001). Meanwhile, the DC value in the left medial frontal gyrus demonstrated significantly negative correlations with RNFL (R = - 0.544, P = 0.013) and MDVF (R = - 0.481, P = 0.032). CONCLUSIONS: NVG exhibited decreased network degree centrality in visual and sensorimotor brain regions and increased degree centrality in cognitive-emotional processing brain region. Additionally, the DC alterations might be complementary imaging biomarkers to assess disease severity.


Assuntos
Glaucoma Neovascular , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Emoções
19.
Neurosurg Rev ; 46(1): 240, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698750

RESUMO

Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the efficacy and safety of OCU. A systematic review and meta-analysis of the published literature on this topic from 2003 to 2023 were conducted in accordance with the PRISMA guidelines. Rigorous statistical analysis with a p-value was performed for related change in visual improvement, gross total resection (GTR), visual deterioration, and olfactory nerve damage. The study included 15 articles with 384 patients in whom OCU was performed by the transcranial approach (TCA) or the endoscopic endonasal approach (EEA). Of these, 341 patients had preoperative visual loss, and 266 patients had postoperative visual recovery. The overall rate of visual improvement was 0.803 (95% CI: 0.733-0.874, p < 0.01). The rate of visual improvement in the EEA and TCA groups was 0.884 (95% CI: 0.803-0.965, p < 0.01) and 0.788 (95% CI: 0.700-0.875, p < 0.01). Further analysis of classification shows that the rate of visual improvement in Type I: < 2 cm was 0.889(95% CI: 0.739-0.969), Type II:2-4 cm was 0.844(95% CI: 0.755-0.910), Type III: > 4 cm was 0.500(95% CI: 0.068-0.932) and the total was 0.853(95% CI: 0.779-0.927 p < 0.01) with low heterogeneity of I2 = 20.80%.Twelve studies separately reported GTR with OCU was 293; the rate of GTR was 0.911 (95% CI: 0.848-0.961, p < 0.01). And the rate of GTR in Type I: < 2 cm was 0.933(95% CI: 0.817-0.986), Type II:2-4 cm was 0.880(95% CI: 0.800-0.936), Type III: > 4 cm was 0.600(95% CI: 0.147-0.947). The total was 0.897(95% CI: 0.830-0.965 p < 0.01) with low heterogeneity of I2 = 34.57%. The related complications of OCU were visual deterioration and olfactory nerve damage. Visual decline was reported in nine studies, and the rate was 0.077 (95% CI: 0.041-0.113, p < 0.01). Six studies reported olfactory nerve damage, and the overall rate was 0.054 (95% CI: 0.019-0.090, p < 0.01). OCU could significantly recover preoperative impaired vision and make GTR easier to achieve, which was also a safe and effective technique in TSM.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Humanos , Meningioma/cirurgia , Período Pós-Operatório , Neoplasias da Base do Crânio/cirurgia , Neoplasias Meníngeas/cirurgia
20.
Sensors (Basel) ; 23(8)2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37112368

RESUMO

With the development of underwater navigation and underwater communication, it remains difficult to obtain time delay measurements after propagating long distance. This paper proposes an improved high-accuracy time delay measuring method for long distance underwater channel propagation. First, by sending an encoded signal, the signal acquisition is carried out at the receiving end. Then, to improve signal to noise ratio (SNR), bandpass filtering is carried out on the receiving end. Next, considering the random changes in the underwater sound propagation channel, a strategy is proposed to select the optimal time window for cross-correlation. Then, new regulations are proposed to calculate the cross-correlation results. To verify the effectiveness of the algorithm, we compared it with other algorithms under low SNR conditions using Bellhop simulation data. Finally, the accurate time delay is obtained. With underwater experiments over different distances, the method proposed by the paper achieves high accuracy. The error is about 10-3 s. The proposed method makes a contribution to underwater navigation and communication.

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